Sustained release systems have been developed over the past several years based on a broad range of technologies, directed to the delivery of a wide selection of pharmaceutical agents. The physical formats for such systems include use of microparticles, slabs or similar macroscopic systems designed for implantation, gels and emulsions, and other preparations conceived to preserve the active agent in the delivery system for an extended period of time.
The mechanism of release for matrix-type sustained release systems is generally understood to occur by hindered diffusion of the active agent through the carrier matrix, or by erosion of the matrix over time resulting in the liberation of the incorporated active agent. These processes are not mutually exclusive, and both mechanisms may be simultaneously active in the case of a given system.
In recent years sustained release devices have been used for the delivery of protein pharmaceutical agents, primarily as a result of the availability of recombinant proteins which have been developed for therapeutic applications in a wide variety of pathological conditions. Development of such systems creates greater challenges to overcome than in the case of low molecular weight drugs and pharmaceutically active substances, since proteins inherently have only marginal conformational stability, and can frequently be susceptible to conditions or processes which result in inactivation or denaturation. In contrast to the degradation or deterioration of low molecular weight pharmaceuticals, the structural alterations in proteins leading to inactivation need not involve changes in the covalent structure of the protein, but can be entirely the consequence of a disruption of an extensive system of non-covalent interactions and/or a disruption of disulfide bonds which are responsible of the preservation of the native three dimensional structure of the protein. This greater lability of proteins, as compared to low molecular weight drugs and other pharmaceutically active substances, creates the need for formulations able to deliver active peptides/proteins in vivo continuously for prolonged time periods.